Serafini-Cessi Franca, Monti Angela, Cavallone Daniela
Department of Experimental Pathology, University of Bologna, Italy. serafini@.alma.unibo.it
Glycoconj J. 2005 Nov;22(7-9):383-94. doi: 10.1007/s10719-005-2142-z.
Tamm-Horsfall glycoprotein (THGP), produced exclusively by renal cells from the thick ascending limb of Henle's loop, is attached by a glycosyl-phosphatidylinositol (GPI)-anchor to the luminal face of the cells. Urinary excretion of THGP (50-100 mg/day) occurs upon proteolytic cleavage of the large ectodomain of the GPI-anchored form. N-Glycans, consisting of a large repertoire of sialylated polyantennary chains and high-mannose structures, account for approximately 30% of the weight of human urinary THGP. We describe: (i) the involvement of urinary THGP high-mannose glycans in defense against infections of the urinary tract, caused by type-1 fimbriated Escherichia coli, which recognize high-mannose structures, (ii) the role of GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-4GlcNAcbeta1-3Gal (Sd(a) determinant) carried by human THGP in protecting the distal nephron from colonization of type-S fimbriated E. coli which recognise NeuAcalpha2-3Gal, (iii) the inhibitory effect of sialylated THGP on crystal aggregation of calcium oxalate and calcium phosphate, thus preventing nephrolithiasis. Finally, we outline the importance of N-glycans in promoting the polymerization of THGP, a process resulting in the formation of homopolymers with an M(r) of several million in urine. Since THGP defense against diseases of the urinary tract mainly consists in binding damaging agents, its ability to behave as a multivalent ligand significantly enhances this protective role.
Tamm-Horsfall糖蛋白（THGP）仅由髓袢升支粗段的肾细胞产生，通过糖基磷脂酰肌醇（GPI）锚定在细胞的管腔面。GPI锚定形式的大胞外域经蛋白水解切割后，THGP会以50 - 100毫克/天的量随尿液排出。N -聚糖由大量唾液酸化多天线链和高甘露糖结构组成，约占人尿THGP重量的30%。我们描述了：（i）尿THGP高甘露糖聚糖在抵御由1型菌毛大肠杆菌引起的尿路感染中的作用，该菌能识别高甘露糖结构；（ii）人THGP携带的GalNAcbeta1 - 4(NeuAcalpha2 - 3)Galbeta1 - 4GlcNAcbeta1 - 3Gal（Sd(a)决定簇）在保护远端肾单位免受能识别NeuAcalpha2 - 3Gal的S型菌毛大肠杆菌定植中的作用；（iii）唾液酸化THGP对草酸钙和磷酸钙晶体聚集的抑制作用，从而预防肾结石。最后，我们概述了N -聚糖在促进THGP聚合中的重要性，这一过程导致在尿液中形成分子量达数百万的同聚物。由于THGP对泌尿系统疾病的防御主要在于结合损伤因子，其作为多价配体的能力显著增强了这种保护作用。
